Mechanism of Aging Flashcards
Define aging
failure to maintain homeostasis under conditions of physiological stress accompanied by a decreased viability and increased vulnerability of the individual
True or false? aging is the most important risk for most chronic diseases
true
This is a group of effects which lead to a decreasing expectation of life with increasing age
senescence
In recent history, the documented age of human has not exceeded ____ years, which means it’s probably an upper limit for natural aging
122
Studies have suggested that life-span is determined ___-___% by genetics
30-35
Organisms as diverse as fruit flies and monkeys when placed on calorie restricted diets show up to a ___% increase in maximum life spans
50
The ____-__ mutant of C. elegant has maximum life-span increased by 100% due to having a slower metabolism
age-1 (single gene mutation in PI3 Kinase homolog)
In mice, caloric restriction coupled with an insulin/IGF pathway mutation can ____ lifespan
double
Fibroblasts having a limited proliferative capacity in vitro of about 50 population doublings is known as the ____ limit
Hayflick
Describe the error or “wear and tear” hypothesis of aging
damage to cellular structure eventually leads to cell death
Describe the programmed cell death hypothesis of aging
senescence inducing genes limit life span of cells
A strong correlation exits between metabolic rate and rate of aging in certain species. Cold blooded species show ____ life span when metabolic rate is decreased by temperature
increased
In regards to waste product accumulation, this is non-enzymatic glycosylation of long lived proteins which leads to oxidized, cross linked products which accumulate within cells as they age.
lipofuscin
Damage to DNA accumulates with age due to inadequate DNA repair processing with age. This increases the incidence of _____
cancer
Free radicals have been thought to be correlated with aging. Where are most free radicals generated?
mitochondria
note: cellular functional impairment occurs when oxygen radicals overwhelm natural cellular antioxidant defenses
True or false? current evidence supports anti-oxidant supplementation as a major means to prevent age-related pathology
false; it does NOT support this
This is the enzyme responsible for synthesizing telomeres. This enzyme is present in the germ cell line, but not somatic cells
telomerase
Overexpression of telomerase in mice increases lifespan, but only in ____-resistant mice
cancer
Oxidative phosphorylation declines with age. True or false?
true - mitochondria function declines with age
Overexpression of mitochondrial catalase in mice leads to a 20% _____ in maximum life span
increase
note: supports mitochondrial function (oxidative phosphorylation)
Autophagy - cellular self-digestion (supply nutrients and remove damaged proteins) ____ with aging
declines
Proponents of this hypothesis say aging is just an extension of the developmental program - a death program that kicks in during the post-reproductive years
program hypothesis
What is the problem with the program hypothesis?
there can be no genetic selective advantage to decreased or increased lifespan for post-reproductive age
What mutation causes Werner’s syndrome and how does it present?
mutation: DNA helicase
symptoms: gray hair before 27, bilateral cataracts, osteoporosis, death by late 40’s
What mutation causes Hutchison-Gilford Progeria Syndrome and how does it present?
mutation: lamin A - nuclear structural gene involved in chromosome maintenance/DNA repair
symptoms: stroke or heart attack by 13, children resemble aging traits of an 80 yo
_____ is produced in the liver in response to growth hormone secretion from the pituitary gland It activates a signaling pathway that inactivates FoxO TFs
IGF-1
IGF-1 mutants seem to be linked to protection of mitochondria from ____ ____
oxidative damage
_____ is a major complex of proteins which monitors nutrients and stress in the cell
TOR
TOR kinase regulates proteins synthesis in the cell in response to stress and nutrient levels. TOR kinase inhibition is linked to what?
increased longevity
AMP kinase is a nutrient and energy sensor that represses ____ pathways when the cell’s AMP/ATP ratio rises
anabolic
AMP kinase acts on _____ TF’s which regulate energy metabolism and longevity
FoxO
_____ activates AMP kinase and can extend lifespan in mice
Metformin
This group of proteins are linked to regulation of metabolism due to the fact that they have NAD-dependent deacetylase activity. They regulate genes linked to switches in metabolism and their activity changes during aging.
Sirtuins
Humans have ___ SIRT genes
7
SIRT 1 is linked to what?
IGF-1, autophagy, and mitochondria biosynthesis
Chronic inflammation plays a role in the progression of age related diseases. ____ cells secrete interleukins
Senescent
Which vitamin has multiple anti-aging qualities?
Vitamin D
